Trial NCT04368728
Publication Walsh E, N Engl J Med, 2020
Dates: 04/05/2020 to 22/06/2020
Funding: Private (BioNTech, Pfizer)
Conflict of interest: Yes

Methods
RCT
Location : Multicenter / United States
Follow-up duration (months): 1.68
18–55y • 10 μg BNT162b1 (n = 12) • 20 μg BNT162b1 (n = 12) • 30 μg BNT162b1 (n = 12) • 100 μg BNT162b1 (n = 12) • Placebo 1 (n = 12) • 10 μg BNT162b2 (n = 12) • 20 μg BNT162b2 (n = 12) • 30 μg BNT162b2 (n = 12) • Placebo 2 (n = 9) 65–85y • 10 μg BNT162b1 (n = 12) • 20 μg BNT162b1 (n = 12) • 30 μg BNT162b1 (n = 12) • Placebo 3 (n = 9) • 10 μg BNT162b2 (n = 12) • 20 μg BNT162b2 (n = 12) • 30 μg BNT162b2 (n = 12) • Placebo 4 (n = 9)
Inclusion criteria
  • Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase). Note that participants <18 years of age cannot be enrolled in the EU. Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study. Participants who, in the judgment of the investigator, are at risk for acquiring COVID-19.Capable of giving personal signed informed consent.
Exclusion criteria
  • Key exclusion criteria were known infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
  • an immunocompromised condition
  • a history of autoimmune disease
  • a previous clinical or microbiologic diagnosis of Covid-19
  • the receipt of medications intended to prevent Covid-19
  • any previous coronavirus vaccination
  • positive test for SARS-CoV-2 IgM or IgG at the screening visit
  • and positive nasal-swab results on a SARS-CoV-2 nucleic acid amplification test within 24 hours before the receipt of trial vaccine or placebo.
Interventions
Intervention
3 IM doses of 10-μg BNT162b1 per dose on days 1, 21
2 IM doses of 20-μg BNT162b1 per dose on days 1, 21
2 IM doses of 30-μg BNT162b1 per dose on days 1, 21
2 IM doses of 100-μg BNT162b1 per dose on days 1, 21
2 IM doses of 10-μg BNT162b2 per dose on days 1, 21
2 IM doses of 20-μg BNT162b2 per dose on days 1, 21
2 IM doses of 30-μg BNT162b2 per dose on days 1, 21
Control
2 IM doses of 0.5 mL normal saline per dose on days 1 and 212 IM doses of 0.5 mL normal saline per dose on days 1 and 21
Participants
Randomized
195 participants
Characteristics of participants
Type of participants: Healthy volunteers
N=195
83 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 0
Mean age:
Age range: 24-82
Description of participants
Healthy SARS-CoV-2 serology/DNA negative adults in four centres in USA
Primary outcome
In the register
Percentage of participants in Phase 1 with local reactions, systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ], adverse events [ Time Frame: From dose 1 through 1 month after the last dose ], serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ], abnormal hematology and chemistry laboratory values [ Time Frame: 1 day and 7 days after dose 1 and 7 days after dose 2 ], grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 1 day and day 7 after dose 1,  7 days after dose 2 ]
In the report
The primary end points in phase 1 of this trial were solicited local reactions (i.e., specific local reactions as prompted by and recorded in an electronic diary), systemic events, and use of antipyretic or pain medication within 7 days after the receipt of vaccine or placebo, as prompted by and recorded in an electronic diary; unsolicited adverse events and serious adverse events (i.e., those reported by the participants, without electronic diary prompts), assessed from the receipt of the first dose through 1 month and 6 months, respectively, after the receipt of the second dose; clinical laboratory abnormalities, assessed 1 day and 7 days after the receipt of vaccine or placebo; and grading shifts in laboratory assessments between baseline and 1 day and 7 days after the first dose and between 2 days and 7 days after the second dose.
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated: Yes
Data accessibility: NR
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Low
General comment In addition to the published article, the trial registry, study protocol, statistical analysis plan, and supplementary appendices were used in data extraction and assessment of risk of bias. This trial was the Phase 1 portion of an ongoing Phase 1/2/3 study. Study recruitment achieved the predetermined sample size. Participants in the 100 µg group did not receive the second dose due to reactogenicity after the first dose. Immunogenicity outcomes were not reported for all arms at all timepoints.